The present invention relates to Magnetic Resonance Imaging (MRI) and, more particularly, to a method of selective excitation so as to improve contrast in Magnetic Resonance Imaging of, for example, connective and other tissues.
Magnetic Resonance Imaging (MRI) is a method to obtain an image representing the chemical and physical microscopic properties of materials, by utilizing a quantum mechanical phenomenon, named Nuclear Magnetic Resonance (NMR), in which a system of spins, placed in a magnetic field resonantly absorb energy, when applied with a certain frequency.
A nucleus can experience NMR only if its nuclear spin I does not vanish, i.e., the nucleus has at least one unpaired nucleon. Examples of non-zero spin nuclei frequently used in MRI include 1H (I=½), 2H (I=1), 23Na (I= 3/2), etc. When placed in a magnetic field, a nucleus having a spin I is allowed to be in a discrete set of energy levels, the number of which is determined by I, and the separation of which is determined by the gyromagnetic ratio of the nucleus and by the magnetic field. Under the influence of a small perturbation, manifested as a radiofrequency magnetic field, which rotates about the direction of a primary static magnetic field, the nucleus has a time dependent probability to experience a transition from one energy level to another. With a specific frequency of the rotating magnetic field, the transition probability may reach the value of unity. Hence at certain times, a transition is forced on the nucleus, even though the rotating magnetic field may be of small magnitude relative to the primary magnetic field. For an ensemble of spin I nuclei the transitions are realized through a change in the overall magnetization.
Once a change in the magnetization occurs, a system of spins tends to restore its magnetization longitudinal equilibrium value, by the thermodynamic principle of minimal energy. The time constant which control the elapsed time for the system to return to the equilibrium value is called “spin-lattice relaxation time” or “longitudinal relaxation time” and is denoted T1. An additional time constant, T2 (≦T1), called “spin-spin relaxation time” or “transverse relaxation time”, controls the elapsed time in which the transverse magnetization diminishes, by the principle of maximal entropy. However, inter-molecule interactions and local variations in the value of the static magnetic field, alter the value of T2, to an actual value denoted T2*.
In MRI, a static magnetic field having a predetermined gradient is applied on an object, thereby creating, at each region of the object, a unique magnetic field. By detecting the NMR signal, knowing the magnetic field gradient, the position of each region of the object can be imaged.
In MRI, pulse sequences are applied to the object (e.g., a patient) to generate NMR signals and obtain information therefrom which is subsequently used to reconstruct images of the object. The above mentioned relaxation times and the density distribution of the nuclear spin are properties which vary from one normal tissue to the next, and from one diseased tissue to the next. These quantities are therefore responsible for contrast between tissues in various imaging techniques, hence permitting image segmentation.
A common characteristic for all of these techniques is that the properties of water molecules are measured, which properties are indirectly dependent on interaction with macromolecules such as proteins.
Connective tissues, such as ligaments, tendons and cartilage appear in standard magnetic resonance (MR) images with low signal-to-noise (S/N) ratio (SNR) due to the water long T2 relaxation times. Images performed with short echo time (TE), result in a significant loss of contrast. In addition to the need to enhance the NMR signal of connective tissues, it is also important to increase the contrast between the different compartments within a specific tissue and between adjacent tissues.
A more modern method is the Magnetization Transfer Contrast (MTC) method [T. D. Scholz, R. F. Hyot, J. R. DeLeonardis, T. L. Ceckler, R. S. Balaban, Water-macromolecular proton magnetization transfer in infracted myocardium: a method to enhance magnetic resonance image contrast, Magn. Reson. Med 1995; 33:178-184; M. L. Gray, D. Burstein, L. M. Lesperance, L. Gehrke, Magnetization transfer in cartilage and its constituent macromolecules, Magn. Reson. Med. 1995; 34: 319-325; R. M. Henkelman, X. Huang, Q.-S. Xiang, G. J. Staniz, S. D. Swanson, M. J. Bronskill, Quantitative interpretation of magnetization transfer, Magn. Reson. Med. 1993; 29:759-766]. According to the MTC method, the contrast between tissues is increased by physical means rather than chemical means. For this technique to be effective, there must be at least two spin systems in the imaged anatomy which are capable of exchanging energy between themselves and one of the systems must have a transverse relaxation time which is shorter than that of the other system. A typical example for such two spin systems is protein, with a short T2, and water with a long T2.
Due to the inverse relationship between T2 and the NMR spectral linewidth, a broad peak would be observed from the protein and a narrow peak would be observed from the water, had the two systems been imaged separately. However, when these systems are analyzed simultaneously, the signal from the protein spread out over the entire image and will not be visible. According to the MTC method, an appropriate pulse sequence is applied so as to saturate the protein spin system and not the water. Consequently, water molecules being in contact with the protein are capable of exchanging magnetization with the protein. Hence, saturating the protein ensures contrast between water being in contact with the protein and water being far from the protein.
Although MTC is a method which is more directly dependent on the nature of the proteins, it has two major drawbacks. First, in MTC signals indicating magnetization transfer from the protein to the water are entangled with signals indicating direct excitation of the water molecules. Secondly, the long time scale in MTC prevents independent measurement of the protein relaxation time T2, and of intramolecular processes within the proteins, such as spin diffusion.
Other methods developed to meet the above requirements of contrast increment, include heavily T1 weighted imaging [R. J. Scheck, A. Romagnolo, R. Hiemer, T. Pfluger, K. Wilhelm, K. Hahn, The carpal ligaments in MR arthrography of the wrist: correlation with standard MRI and wrist arthroscopy, J. Magn. Reson. Imag. 1999; 9:468-474], fat suppression [C. G. Peterfy, S. Majumdar, P. Lang, C. F. van Dijke, K. Sack, H. K. Ganant, MR Imaging of the arthritic knee: improved discrimination of cartilage, synovium, and effusion with pulsed saturation transfer and fat-suppressed T1-weighted sequences, Radiology 1994; 191:413-419], diffusion weighted imaging [Y. Xia, T. Farquhar, N. Burton-Wurster, E. Ray, L. Jelinski, Diffusion and relaxation mapping of cartilage-bone plugs and excised disk using micromagnetic resonance imaging, Magn. Reson. Med. 1994; 31:273-282] and projection reconstruction techniques that achieve much shorter echo time than conventional methods [G. E. Gold, J. M. Pauly, A. Macovsky, R. J. Herfkens, MR spectroscopic imaging of collagen: tendons and knee menisci, Magn. Reson. Med. 1995; 34:647-654].
Another way to obtain contrast, with specific enhancement for ordered tissues, such as articular cartilage and tendons, is Double Quantum Filter [Tsoref, H. Shinar, Y. Seo, U. Eliav, G. Navon, Proton Double Quantum Filtered MRI—A New Method for Imaging Ordered Tissues, Magn. Reson. Med. 1998; 40:720-726; U. Eliav and G. Navon, A Study of Dipolar Interactions and Dynamic Processes of Water Molecules in Tendon by 1H and 2H Homonuclear and Hetronuclear Multiple-Quantum-Filtered NMR Spectroscopy, J. Magn. Reson. 1999; 137:295-310. This method is based on the residual intramolecular dipolar interaction in water molecules whose motion is restricted by the anisotropy induced by ordered proteins such as collagen fibers. The contrast in DQF MRI stems from the fact that only water molecules associated with ordered structures are detected, and signals originating from molecules in isotropic tissues are suppressed.
While these approaches do increase the MR signal of connective tissues and the contrast between connective and adjacent tissues, the results are not yet optimal for diagnostic purposes.
There is thus a widely recognized need for, and it would be highly advantageous to have, a method of magnetic resonance imaging devoid of the above limitations, including the observed signal reflecting to the first order water solvent properties, rather than those of proteins.